Development and Validation of a UHPLC-MS/MS Method for the Simultaneous Quantification of Candesartan and Bisoprolol Together with Other 16 Antihypertensive Drugs in Plasma Samples.

Antihypertensive pharmacological therapy is often characterized by a coadministration of different classes of drugs. Therefore, analytical methods allowing the simultaneous quantification of many drugs are needed for therapeutic drug monitoring (TDM) purposes in this context. In particular, TDM represents a useful tool to discriminate poor adherence from real cases of resistant hypertension.

A genome-wide association study of European advanced cancer patients treated with opioids identifies regulatory variants on chromosome 20 associated with pain intensity.

Background: Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids.

Endogenous plasma resuspension of peripheral blood mononuclear cells prevents preparative-associated stress that modifies polyA-enriched RNA responses to subsequent acute stressors.

Human peripheral blood mononuclear cells (PBMCs) are used to examine biological processes and disease, when basal variability in cellular activation and splicing is described and unexplained. Using isolation systems that maintained buffy coat cells (PBMCs, platelets) in their own plasma, poly-A enriched RNA-sequencing (RNASeq) detected 42,720 Ensembl gene IDs, including >95% of the top 100 Genotype Tissue Expression Project (GTEx)-expressed genes in lung, colon, heart, skeletal muscle and liver, and 10/17 clinically-actionable genes listed by the Pharmacogenomics Knowledgebase. Transcriptome changes were defined after 1h treatment with 32°C hypothermia (hsp70 family member change), 10 μmol/L ferric citrate that had no discernible effect, and 100 μg/mL cycloheximide leading to induction of primary response (immediate early) genes including IL1B and TNF.

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?

Aims: To examine the associations between and polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.

Patients & Methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.

Genetic polymorphisms influencing antihypertensive drug responses.

Hypertension is a major contributor to cardiovascular disease and its associated morbidity and mortality. The low efficacy observed with some anti-hypertensive therapies has been attributed partly to inter-individual genetic variability. This paper reviews the major findings regarding these genetic variabilities that modulate responses to anti-hypertensive therapies such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers (CCBs) and β-adrenoceptor blockers.

Clinical Application of Pharmacogenomics in the Administration of Common Cardiovascular Medications.

Introduction: Genomic variations among individuals can greatly affect their responses to different medications. Pharmacogenomics is the area of study that aims to understand the relationship between these various genetic variations and subsequent drug responses. Many medications used to optimize cardiovascular health are affected by these genetic variants and these relationships can subsequently impact dosing strategies in patients.

OSGEP regulates islet β-cell function by modulating proinsulin translation and maintaining ER stress homeostasis in mice.

Proinsulin translation and folding is crucial for glucose homeostasis. However, islet β-cell control of Proinsulin translation remains incompletely understood. Here, we identify OSGEP, an enzyme responsible for tA modification of tRNA that tunes glucose metabolism in β-cells.

Impact of ABCB1 single-nucleotide variants on early, extremely severe neutropenia induced by paclitaxel/nanoparticle albumin-bound paclitaxel in patients with gastric cancer.

Aims: Paclitaxel and nanoparticle albumin-bound (nab)-paclitaxel can cause early, extremely severe neutropenia, occasionally leading to fatal outcomes. As paclitaxel is a substrate of P-glycoprotein, this study aimed to investigate the impact of ABCB1 single-nucleotide variants, which encode P-glycoprotein, on early, extremely severe neutropenia in patients receiving paclitaxel/nab-paclitaxel plus ramucirumab as second-line therapy for unresectable advanced/recurrent gastric cancer.

Methods: We analysed patients treated at Aichi Cancer Center Hospital from January 2018 to August 2023, with DNA samples stored in the Cancer BioBank Aichi.

Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index.

Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial.

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis).

Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential.

Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear.

Allele frequency of genetic variations related to the gene-drug pair in a group of Iranian population.

Objectives: The efficacy and safety of drug treatments vary widely due to genetic variations. Pharmacogenomics investigates the impact of genetic variations on patient drug response. This research investigates the frequency of genetic variations in the Iranian population, comparing them with global data to provide insights into the pharmacogenomic approach in the Iranian population.

Functional analysis of G6PD variants associated with low G6PD activity in the All of Us Research Program.

The glucose-6-phosphate dehydrogenase (G6PD) enzyme protects red blood cells against oxidative damage. Individuals with G6PD-impairing polymorphisms are at risk of hemolytic anemia from oxidative stressors. Prevention of G6PD deficiency-related hemolytic anemia is achievable by identifying affected individuals through G6PD genetic testing.

Sex differences in insulin induced hippocampus functional connectivity during visual food cue presentation.

Aims: Central insulin has been shown to regulate eating behavior and cognitive processes in a sex-specific manner. Besides memory, the hippocampus is pivotal in the control of appetite. However, how insulin interacts with the hippocampal food cue response and the role of sex hormones in this context remain unclear.

Methadone metabolism and cytochrome P450 polymorphisms: a systematic review and meta-analysis.

Introduction: Confusion regarding methadone metabolism exists, hampering optimal clinical use. A systematic review was conducted to assess the impacts of cytochrome P450 (CYP) genetic polymorphisms on methadone outcomes.

Methods: MEDLINE, EMBASE, Web of Science, PsycINFO, and CENTRAL were searched to identify studies reporting methadone dose-adjusted plasma concentrations, clearance, maintenance dose, or treatment response in relation to polymorphisms in humans.

Assessment of knowledge, perceptions, and readiness of healthcare professionals towards clinical pharmacogenomics implementation in Qatar: a mixed-method study.

Introduction: Pharmacogenomics implementation in clinical practice is anticipated to improve our understanding of individual variations in drug response and optimise the safety and efficacy of drug therapy. We aimed to assess the knowledge, perceptions, and readiness of physicians, pharmacists, and nurses in Qatar regarding the implementation of clinical pharmacogenomics.

Methods: A mixed-method study with an explanatory sequential design was conducted.

International Consensus Statement on Platelet Function and Genetic Testing in Percutaneous Coronary Intervention: 2024 Update.

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient.

The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment.

Given the high prevalence of breast cancer and the diverse genetic backgrounds of patients, a growing body of research emphasizes the importance of pharmacogenetic-based pharmacokinetic analysis in optimizing treatment outcomes. The treatment of breast cancer involves multiple drugs whose metabolism and efficacy are influenced by individual genetic variations. Genetic polymorphisms in drug-metabolizing enzymes and transport proteins are crucial in the regulation of pharmacokinetics.

Afro-Latin American Pharmacogenetics of , , and in Dominicans: A Study from the RIBEF-CEIBA Consortium.

: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines , , and alleles and genotypes in 197 healthy volunteers from the Dominican Republic, as part of the RIBEF-CEIBA collaborative network. : The analysis focuses on the participants' tri-hybrid genomic ancestry, with CYP alleles determined by real-time PCR and molecular ancestry inferred using 90 AIMs.

MIR27A rs895819 CC Genotype Severely Reduces miR-27a Plasma Expression Levels.

rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression.